Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The incidence of elevated serum levels of immunoreactive calcitonin (CT) in human myeloproliferative and lymphoproliferative disorders was investigated. On the basis of twice the normal range, about 45% of patients with acute leukemia and blast crisis of chronic myelocytic leukemia (CML) showed elevated serum levels of CT. Markedly elevated levels (greater than 1,000 pg/ml) were only found in this group. Since immunoreactive CT dropped to normal or only slightly elevated levels in remission and increased again before or during relapse, serum CT levels seem to reflect the activity of the disease. However, in patients with chronic leukemia, Hodgkin's and non-Hodgkin's lymphoma, a lower incidence and only slightly elevated serum levels were found. In addition, the molecular weight of the proteohormone in serum specimen and cell extracts was investigated by gel chromatography. Besides physiological CT, different high-molecular weight forms of the hormone could be demonstrated in serum and in cell extracts. Extracts of leukemic cells revealed higher molecular forms only. It is suggested that the proteohormone is ectopically produced by leukemic cells.
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PMID:Ectopically produced calcitonin in human hemoblastoses. 712 Aug 75

A chromosomally abnormal clone is demonstrable in the bone marrow of a significant number of patients with hemic disorders that carry an increased risk for the subsequent development of leukemia. These "preleukemia" states include a variety of cytopenias, myeloproliferative disorders, and childhood syndromes. The cytogenetic alterations that occur nonrandomly in these dyscrasias are often similar to those observed in acute nonlymphocytic leukemia and in the accelerated phase of chronic granulocytic leukemia: monosomy for chromosome 7; trisomy for 8,9,21, and the long arm of 1(1q); deletions of 5 and 20 (5q-, 20q-); and an isochromosome derived from 17 (iso 17q). These findings support the view that despite clinical differences, these various preleukemic disorders are all characterized by the presence in the hematopoietic tissues of a clone of cells derived from an altered hemic stem cell. Furthermore, the data suggest that preleukemia, chronic leukemia, and acute leukemia may be fundamentally similar diseases, differing primarily in the rate at which the aberrant clone is expanding. Chromosome studies may be of prognostic value in the cytopenic preleukemias. Patients with abnormalities show a decreased survival and are at increased risk for progression to acute nonlymphocytic leukemia. In the myeloproliferative disorders and the preleukemic childhood disorders, cytogenetic alterations are not clearly predictive, and aberrant clones may persist for years without clinical progression.
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PMID:Preleukemias. 727 93

Acute graft-versus-host disease (aGVHD) has been classified according to the Seattle criteria as grades 0, I, II, III, and IV for 20 years. The predictive value of such detailed grading is a matter of debate; publications usually report GVHD as present or absent or as absent, moderate, or severe. The Working Party Chronic Leukemia of the European Group for Bone Marrow Transplantation analyzed data of 1,294 patients transplanted from an allogeneic donor for chronic myelogenous leukemia (CML) in first chronic phase and tested the predictive value of aGVHD grading for the following end-points: day 100 mortality (D100M), transplant-related mortality (TRM), relapse incidence (RI), leukemia-free survival (LFS), and survival (SURV). aGVHD was absent in 462 patients (35.7%), grade I occurred in 335 (25.8%), grade II in 264 (20.5%), grade III in 110 (8.5%), and grade IV in 123 patients (9.5%). A total of 297 patients (23%) died within 100 days, 495 patients (38%) died of any TRM, and 100 patients (8%) died of relapse. D100M according to grades 0, I, II, III, and IV was 17%, 13%, 19%, 38%, and 70%, respectively, with significant difference between 0-II versus III-IV. TRM was 28%, 27%, 43%, 68%, and 92%, respectively, with a distinct separation between 0-I versus II-IV. RI showed a continuous decrease of 37%, 30%, 23%, 18%, and 8%, respectively, with increasing aGVHD. LFS was 45%, 51%, 44%, 26%, and 7%, respectively, and was best for patients with grade I aGVHD. This finding was also reflected in a better overall survival (60%, 64%, 53%, 30%, and 8%, respectively). The better LFS for grade I aGVHD patients compared with patients with grade 0 or II aGVHD was confirmed (P = .05) in a multivariate analysis. These data document the value of the present 5-point grading of aGVHD, ie, different outcome is observed depending on endpoint analyzed. Restricting information about aGVHD to presence or absence is not warranted.
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PMID:Acute graft-versus-host disease: grade and outcome in patients with chronic myelogenous leukemia. Working Party Chronic Leukemia of the European Group for Blood and Marrow Transplantation. 760 12

The immune reactivity of allogeneic lymphocytes plays a major role in the control of leukemia after bone marrow transplantation. In patients with recurrent leukemia after marrow transplantation, chimerism and tolerance provide ideal conditions for adoptive immunotherapy with donor lymphocytes. We studied the effect of donor lymphocyte transfusions on acute and chronic leukemia in relapse after bone marrow transplantation. One hundred thirty-five patients with chronic myeloid leukemia (CML) (N = 84), acute myeloid leukemia (AML) (N = 23), acute lymphoblastic leukemia (ALL) (N = 22), myelodysplastic syndrome (MDS) (N = 5), and polycythemia vera with osteomyelofibrosis (PCV) (N = 1) were treated with transfusions of donor lymphocytes. Patients were monitored for response of leukemia, including in CML, the use of the polymerase chain reaction for bcr/abl mRNA transcripts and for the occurrence of graft-versus-host disease (GVHD) and myelosuppression. Complete remissions were induced by donor lymphocyte transfusions in 54 patients with CML (73%) and in the patient with PCV; complete remissions were also induced in five patients (29%) with AML and a patient with MDS. In contrast, ALL did not respond to adoptive immunotherapy with donor lymphocyte transfusions. Remissions were durable in patients treated for CML in chronic phase (probability of remission: 87% at 3 years). Lymphocyte transfusions were also given to 18 patients with ALL, AML, MDS, and transformed phase CML who were in remission after chemotherapy. These remissions were not durable. Fifty-two patients (41%) developed GVHD of grade 2 or more, and 41 patients (34%) showed signs of myelosuppression. Seventeen patients died without leukemia, 14 patients with GVHD and/or myelosuppression. Donor lymphocyte transfusions exert strong effects against myeloid forms of leukemia and induce durable remissions in CML.
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PMID:Graft-versus-leukemia effect of donor lymphocyte transfusions in marrow grafted patients. 861 35

We determined the expression of the multidrug resistance-associated protein (MRP), a new putative transmembrane drug transporter, in peripheral blood cells from healthy volunteers as well as from 60 patients with acute or chronic leukemia, using an RNase protection assay. MRP appeared to be ubiquitously expressed at low levels in all nonmalignant hemopoietic cell types, reflecting its basal constitutive expression. In acute myelocytic leukemia (AML) (n = 16), one of nine untreated patients and two of seven patients with prior chemotherapy showed significant hyperexpression of MRP. In chronic lymphocytic leukemia (CLL) (n = 21), either treated (n = 8) or untreated (n = 13), a high percentage (15 of 21: 71% had relatively high expression levels of the MRP gene. In contrast, low MRP expression levels were detected in acute lymphocytic leukemia (n = 14), and in chronic myelocytic leukemia (n = 9). DNA analysis by Southern blotting did not reveal amplification of the MRP gene in the leukemia samples, including those with elevated MRP mRNA levels. We conclude that relatively high expression of MRP is occasionally observed in AML and at high frequency in CLL, irrespective of treatment, probably due to transcriptional activation and/or increased mRNA stability.
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PMID:Expression of the multidrug resistance-associated protein (MRP) in acute and chronic leukemias. 791 48

Serum ferritin (SF) was estimated using double antibody sandwich ELISA in 83 patients of acute and chronic leukemia at various stages of the disease. In 35 patients of acute lymphoblastic leukemia (ALL) in remission, the SF levels fell significantly from 550.63 ng/ml at presentation to 319.56 ng/ml but remained significantly higher than the control values of 46.14 ng/ml. In 28 patients of acute myeloid leukemia (AML), the SF values at 775.0 ng/ml were much higher than those in ALL patients and showed no decline with remission. This pattern was also seen in patients of chronic myeloid leukemia in blast crisis (CML-BC) with SF levels of 804.03 ng/ml at presentation and 717.43 ng/ml at partial remission. The values of SF were lowest in patients of CML in chronic phase ranging from 271.5 ng/ml to 332.12 ng/ml and showed no relationship with variation in total leucocyte count. No correlation was found between SF values and various clinical and laboratory parameters such as age, sex, fever, organomegaly, haemoglobin and total leucocyte count. Thus, while there appeared to be a correlation between remission and SF values in ALL, no such correlation existed between the activity of the disease and SF in other types of leukemia.
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PMID:Role of serum ferritin in assessment of disease activity in acute & chronic leukemia. 792 58

Although allogeneic bone marrow transplantation has been shown to be a highly effective treatment for acute and chronic leukemia, leukemic relapse remains a significant problem. Leukemic relapse occurs in recipient cells in the majority of cases, but the paucity of donor cell leukemias may reflect the sensitivity of the investigative technique. We have developed a highly sensitive technique to identify the origin of all hematopoietic cells in the post transplant state which is based on PCR amplification of microsatellites, polymorphic tandem repetitive elements. We have identified donor leukemia (AML M5) following a sex matched BMT for severe aplastic anemia, verified a previously reported case of donor leukemia following BMT for chronic granulocytic leukemia and recently identified an acquired cytogenetic abnormality(del 11q23) in donor cells four years following an apparently successful BMT for AML. In all cases the donors have remained healthy. Postulated mechanisms include transfer to the transplanted marrow of a dormant oncogene residing in the DNA of either a virus, the chromosomes of degenerating irradiation damaged host leukemic cells or in the marrow stroma which is radioresistant and host in origin following BMT. Using sensitive techniques donor leukemia has been shown to be a more common event than was previously thought and an understanding of its pathogenesis may allow us to elucidate leukemogenic mechanisms in man.
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PMID:Donor leukemia following allogeneic bone marrow transplantation. 815 80

Cytogenetic and molecular characteristics of chronic myeloid leukemia in blast crisis and Ph-positive acute leukemia are compared. The main differences relate to the presence of Ph-negative metaphases at diagnosis and the disappearance of Ph in complete remission in acute leukemia, and the localization of the chromosome breakpoints in the BCR gene, in the bcr segment in chronic leukemia and in the first intron of the BCR gene in 50% of acute leukemias. The profiles of these abnormalities, as well as the types of additional chromosome changes, are not sufficient to distinguish between the two disorders in every patient. The distinction between these two entities, which is possible in the majority of patients, will be improved by results of experimental work currently in progress in many laboratories.
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PMID:Differences between blastic chronic myeloid leukemia and Ph-positive acute leukemia. 825 2

The number of survivors of childhood leukemia treated with growth hormone for growth retardation is increasing. The debate about the direct or indirect relationship of GH and insulin-like growth factor I (IGF-I) to the occurrence or recurrence of malignancy, especially in the case of GH therapy in patients with leukemia, is still unresolved. We, therefore, studied the effect of GH and IGF-I on bone marrow of patients with acute leukemia (ALL and AML) in diagnosis and recurrence and in chronic leukemia patients (CML) in remission. GH increased blast colony numbers by a mean of 68% and 77% at GH concentrations of 250 and 300 ng/ml, respectively. IGF-I increased blast colony numbers in ALL patients by 50, 93 and 105%, and in AML patients by 33, 58 and 65%, at IGF-I concentrations of 0.05, 0.25 and 0.5 ng/ml, respectively. In 3 CML patients in remission a granulocyte-macrophage colony forming assay did not reveal stimulation of peripheral blood blast colony formation by GH or IGF-I. Our in vitro data (as previously reported) suggest that GH and IGF-I may promote blast cell proliferation, and the supplemental administration of these peptides in leukemia patients in remission must be carefully monitored for early relapse. Additional studies on bone marrow cells of leukemic patients in remission are needed in order to examine the effects of GH and IGF-I on these cells.
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PMID:The effect of growth hormone and IGF-I on clonogenic growth of hematopoietic cells in leukemic patients during active disease and during remission--a preliminary report. 837 94

Allogeneic bone marrow transplantation (BMT) is the treatment of choice for hematologic malignancies resistant to conventional chemotherapy and for patients who are at high risk for relapse. Until recently, no cure could be offered to patients relapsing following allogeneic BMT. We present our long-term observations of the first patient with remission reinduced by allogeneic cell therapy (allo-CT) using donor peripheral blood lymphocytes (PBL). In addition, we review the cumulative international experience with allo-CT used to treat 163 patients, 105 with CML and 58 with other hematologic diseases, who relapsed following allogeneic BMT. The first patient treated by allo-CT was diagnosed with acute resistant pre-B lymphoblastic leukemia (ALL) in extensive third hematologic and extramedullary relapse shortly after BMT. He was given infusions of donor (sister) PBL in multiple increments. Subsequently, he developed mild, reversible graft-vs-host disease (GVHD) in parallel with regression of all hematologic and cytogenetic disease manifestations. More than 8 years after allo-CT, he is disease-free with Karnofsky score 100% and no evidence of residual male cells by PCR. International data show that relapse after BMT was successfully reversed by donor PBL treatment in 97 of 158 evaluable patients; 72/100 (72%) with chronic myeloid leukemia (CML) and 25/58 (44.8%) with other malignant hematologic diseases including acute leukemia, lymphoma, and myelodysplastic syndrome. T cell depletion (TCD) for prevention of GVHD was performed for 60/105 (57%) patients with CML and 31/58 (53.4%) patients with other hematologic malignancies. Complete response after allo-CT was obtained in recipients of both TCD-BMT and unmodified BMT. GVHD due to allo-CT developed in 86/158 (54.4%) of the patients, 63/100 (63.0%) with CML and 23/58 (39.6%) with other hematologic diseases. alpha-interferon (IFN-alpha) was given to 67.9% of patients with CML and 28.1% of patients with other diseases. The cumulative experience shows that allo-CT can successfully reverse chemoradiotherapy-resistant relapse of acute leukemia and even more effectively of chronic leukemia independently of alpha-interferon therapy. Although GVHD was frequent among responders, accompanied occasionally by transient or irreversible marrow aplasia, remissions were also obtained in patients with no GVHD. Allo-CT should therefore be considered as treatment of choice for overt relapse or de novo minimal residual disease post-BMT. Administration of donor peripheral blood lymphocytes in graded increments at an early stage of relapse may be the best approach for combining optimal timing at the stage of minimal disease while controlling and minimizing the risk of GVHD on an individual basis.
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PMID:Allogeneic cell therapy for relapsed leukemia after bone marrow transplantation with donor peripheral blood lymphocytes. 854 46


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